Vascular damage causes platelets to adhere to exposed subendothelial collagen. The adherent platelets release ADP which makes passing platelets "stricky" so that an aggregate is formed. Such aggregates may be either beneficial or harmful because they can promote both hemostasis and thrombosis. (Although thrombin is also involved in hemostasis and thrombosis, we will not study its role or the mechanisms of platelet secretion.) We will elucidate the mechanisms of platelet aggregation using in vitro biochemical and physiological methods. Stimulation of normal platelets with ADP causes the appearance of fibrinogen receptors and aggregation if sufficient fibrinogen is bound. Abnormal platelets which cannot bind fibrinogen also cannot aggregate. We would like to determine how the fibrinogen receptor is induced, to which membrane components the fibrinogen binds, the distribution of bound fibrinogen on platelets in aggregates and of fibrinogen receptors on adherent platelets, the role of membrane fluidity in aggregation, the relationship of aggregability and fibrinogen binding to platelet charge (electrophoretic mobility), and the possible loss of radioactive surface labels from platelets when they aggregate. In addition to normal platelets stimulated with ADP, we will use platelets incubated with chymotrypsin which aggredate on addition of fibrinogen without ADP, and platelets incubated with EDTA which retain many functions but cannot aggregate even after addition of ADP, fibrinogen and calcium.